More than any other species, humans have evolved a remarkable ability to manipulate the physical environment with their hands, resulting in an extraordinary transformation of our culture and our planet. This ability co-evolved with an enormous expansion of the neocortex and an increase in the number of areas of the cortex associated with hand use and hand-eye coordination. Although manual abilities in non-human primates cannot match those of humans, they are nonetheless impressive and rely on similar brain mechanisms. Indeed, most of posterior parietal cortex in both human and non-human primates comprise a network that includes areas 5 and the anterior intraparietal area (AIP), and is devoted to reaching, grasping, manipulation and bimanual coordination, as well as transforming sensory information into a coordinate system in which these actions can be initiated. Three overarching goals of the present proposal are: to assess the role of areas 5 and AIP in executing three well-defined tasks that require a monkey to perform natural (although complex) manual and bimanual behaviors under both visual and non-visual guidance. This will be accomplished by permanently lesioning areas 5 or AIP in different animals and examining the resulting behavioral deficits that arise following lesions to these fields. The second goal is to determine if spared areas in the network that generates complex manual behaviors can compensate for permanent loss of a cortical field. This will be accomplished by utilizing a microfluidic cooling device to reversibly deactivate areas 2 and AIP in the animals with area 5 lesions, or deactivate areas 2 and 5 in the animals with AIP lesions. The final goal is to examine the coordinated activities of areas 5 and AIP for generating complex manual behaviors by rapidly and reversibly deactivating area 5, AIP or 5+AIP ipsilaterally and bilaterally in the same animal and observing resulting behavior. In all cases, functional inputs of the deactivated region will be determined. Our lesions and reversible deactivations will be quantified using a combination of thermal recordings, electrophysiological, behavioral indications, and 3D stereological data reconstructions. These studies build on our previous data on behavioral and cortical plasticity following lesions to posterior parietal cortex. Our proposed studies will define the coordinated role of areas 5 and AIP in normal cortical circuits as well as their capacity to compensate for restricted posterior parietal lesions. PUBLIC HEALTH RELEVANCE: Humans are highly dexterous animals, and bimanual dexterity is critical for even the most rudimentary tasks that humans perform daily. The importance of these abilities is particularly marked when parietal cortical areas that lie at the core of these abilities are lost due to stroke or lesions, and severe deficits such as optic ataxias, dystonias, choreas, and neglect occur. The proposed studies will examine posterior parietal areas involved in manual behaviors, and the behavioral deficits that arise when these areas are lesioned. We will also determine the extent of behavioral recovery and the cortical plasticity that underlies this recovery following progressively larger virtual lesions to posterior parietal cortex.